ORGANIC LETTERS
Diarylprolinol Silyl Ether as Catalyst of an exo-Selective, Enantioselective Diels−Alder Reaction
2007 Vol. 9, No. 15 2859-2862
Hiroaki Gotoh and Yujiro Hayashi* Department of Industrial Chemistry, Faculty of Engineering, Tokyo UniVersity of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
[email protected] Received April 30, 2007
ABSTRACT
In combined use with CF3CO2H, 2-[bis(3,5-bis-trifluoromethylphenyl) triethylsiloxymethyl]pyrrolidine was found to be an effective organocatalyst of an exo-selective, enantioselective Diels−Alder reaction of r,β-unsaturated aldehydes.
Diarylprolinols are a class of small, chiral organic molecules that have proven to be particularly useful in asymmetric synthesis. Diphenylprolinol reacts with a boron reagent to generate chiral oxazaborolidine, which has been widely utilized in the Corey-Bakshi-Shibata (CBS) reduction developed by Corey.1 His group also discovered that chiral oxazaborolidinium ions prepared from diarylprolinols are versatile chiral Lewis acid catalysts, promoting the DielsAlder reaction and the cyanation reaction of aldehydes.2 Enantioselective reactions catalyzed by organocatalyst have (1) (a) Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987, 109, 5551. (b) Corey, E. J.; Bakshi, R. K.; Shibata, S.; Chen, C.-P.; Singh, V. K. J. Am. Chem. Soc. 1987, 109, 7925. (c) For a review, see: Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. 1998, 37, 1986. (2) (a) Corey, E. J.; Shibata, T.; Lee, T. W. J. Am. Chem. Soc. 2002, 124, 3808. (b) Ryu, D. H.; Lee, T. W.; Corey, E. J. J. Am. Chem. Soc. 2002, 124, 9992. (c) Ryu, D. H.; Corey, E. J. J. Am. Chem. Soc. 2003, 125, 6388. (d) Ryu, D. H.; Zhou, G.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 4800. (e) Hu, Q.-Y.; Zhou, G.; Corey, E. J. J. Am. Chem. Soc. 2004, 126, 13708. (f) Zhou, G.; Hu, Q.-Y.; Corey, E. J. Org. Lett. 2003, 5, 3979. (g) Ryu, D. H.; Corey, E. J. J. Am. Chem. Soc. 2005, 127, 5384. (h) Snyder, S. A.; Corey, E. J. J. Am. Chem. Soc. 2006, 128, 740. (i) Hong, S.; Corey, E. J. J. Am. Chem. Soc. 2006, 128, 1346. (j) Yeung, Y.-Y.; Hong, S.; Corey, E. J. J. Am. Chem. Soc. 2006, 128, 6310. (k) Zhou, G.; Corey, E. J. J. Am. Chem. Soc. 2005, 127, 11958. (l) Liu, D.; Canales, E.; Corey, E. J. J. Am. Chem. Soc. 2007, 129, 1498. (m) For a review, see: Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650. 10.1021/ol071009+ CCC: $37.00 Published on Web 06/20/2007
© 2007 American Chemical Society
received a great deal of attention in recent years,3 and silyl ethers of diarylprolinols 4,5,6 have been found to act as effective organocatalysts of various enantioselective transformations, as independently developed by Jørgensen’s4 and (3) (a) Berkssel, A.; Groger, H. Asymmetric Organocatalysis; WileyVCH: Weinheim, Germany, 2005. (b) Dalko, P. I.; Moisan, L. Angew. Chem., Int. Ed. 2004, 43, 5138. (c) Hayashi, Y. J. Synth. Org. Chem. Jpn 2005, 63, 464. (d) List, B. Chem. Commun. 2006, 819. (e) Marigo, M.; Jørgensen, K. A. Chem. Commun. 2006, 2001. (f) Lelais, G. D.; MacMillan, W. C. Aldrichim. Acta 2006, 39, 79. (g) Gaunt, M. J.; Johnsson, C. C. C.; McNally, A.; Vo, N. T. Drug DiscoVery Today 2007, 12, 8. (4) (a) Marigo, M.; Wabnitz, T. C.; Fielenbach, D.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2005, 44, 794. (b) Marigo, M.; Fielenbach, D.; Braunton, A.; Kjasgaard, A.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2005, 44, 3703. (c) Marigo, M.; Franzen, J.; Poulsen, T. B.; Zhuang, W.; Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 6964. (d) Marigo, M.; Schulte, T.; Franzen, J.; Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 15710. (e) Zhuang, W.; Marigo, M.; Jørgensen, K. A. Org. Biomol. Chem. 2005, 3, 3883. (f) Franzen, J.; Marigo, M.; Fielenbach, D.; Wabnitz, T. C.; Kjasgaard, A.; Jørgensen, K. A. J. Am. Chem. Soc. 2005, 127, 18296. (g) Brandau, S.; Landa, A.; Franzen, J.; Marigo, M.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2006, 45, 4305. (h) Brandau, S.; Maerten, E.; Jørgensen, K. A. J. Am. Chem. Soc. 2006, 128, 14986. (i) Carlone, A.; Marigo, M.; North, C.; Landa, A.; Jørgensen, K. A. Chem. Commun. 2006, 4928. (j) Bertelsen, S.; Diner, P.; Johansen, R. L.; Jørgensen, K. A. J. Am. Chem. Soc. 2007, 129, 1536. (k) Bertelsen, S.; Marigo, M.; Brandes, S.; Diner, P.; Jørgensen, K. A. J. Am. Chem. Soc. 2007, 129, 12973. (5) (a) Hayashi, Y.; Gotoh, H.; Hayashi, T.; Shoji, M. Angew. Chem., Int. Ed. 2005, 44, 4212. (b) Gotoh, H.; Masui, R.; Ogino, H.; Shoji, M.; Hayashi, Y. Angew. Chem., Int. Ed. 2006, 45, 6853.
Figure 1. The diphenylprolinol-organocatalysts examined in this study.
our5 groups. We have found that they promote the enantioselective Michael reaction of nitroalkene and aldehyde to afford the adduct with excellent diastereo- and enantioselectivities.5aEnders and co-workers elegantly applied this reaction to a triple-cascade organocatalytic reaction for the synthesis of chiral cyclohexanecarbaldehydes.6i Recently we reported that diphenylprolinol silyl ether catalyzes the enantioselective ene reaction of an R,β-unsaturated aldehyde with cyclopentadiene to afford substituted cyclopentadienes with excellent enantioselectivity (Scheme 1).5b In the course
Scheme 1.
Asymmetric Ene Reaction
of developing this reaction further, we happened to find that an exo- and enantioselective Diels-Alder reaction proceeds on changing the reaction conditions. That is, in the presence of an acid catalyst, the Diels-Alder reaction becomes the principle pathway, affording the exo-isomer with high diastereo- and excellent enantioselectivities. The Diels-Alder reaction is a synthetically powerful method for the construction of regio and stereochemically defined cyclohexane frameworks, key components of a wide (6) Other group’s application of diarylprolinol ether, see; (a) Chi, Y.; Gellman, S. H. Org. Lett. 2005, 7, 4253. (b) Sunden, H.; Ibrahem, I.; Cordova, A. Tetrahedron Lett. 2006, 47, 99. (c) Ibrahem, I.; Cordova, A. Chem. Commun. 2006, 1760. (d) Govender, T.; Hojabri, L.; Moghaddam, F. M.; Arvidsson, P. I. Tetrahedron: Asymmetry 2006, 17, 1763. (e) Chi, Y.; Gellman, S. H. J. Am. Chem. Soc. 2006, 128, 6804. (f) Zu, L.; Li, H.; Wang, J.; Yu, X.; Wang, W. Tetrahedron Lett. 2006, 47, 5131. (g) Wang, W.; Li, H.; Wang, J.; Zu, L. J. Am. Chem. Soc. 2006, 128, 10354. (h) Zhao, G.-L.; Corvoda, A. Tetrahedron Lett. 2006, 47, 7417. (h) Rios, R.; Sunden, H.; Ibrahem, I.; Zhao, G.-L.; Eriksson, L.; Cordova, A. Tetrahedron Lett. 2006, 47, 8547. (i) Enders, D.; Huttl, M. R. M.; Grondal, C.; Raabe, G. Nature 2006, 441, 861. (j) Enders, D.; Huttl, M. R. M.; Runsink, J.; Raabe, G.; Wendt, B. Angew. Chem., Int. Ed. 2007, 46, 467. (k) Vesely, J.; Ibrahem, I.; Zhao, G.-L.; Rios, R.; Cordova, A. Angew. Chem., Int. Ed. 2007, 46, 778. (l) Zhao, G.-L.; Xu, Y.; Sunden, H.; Eriksson, L.; Sayah, M.; Cordova, A. Chem. Commun. 2007, 734. (m) Ibrahem, I.; Rios, R.; Vesely, J.; Zhao, G.-L.; Cordova, A. Chem. Commun. 2007, 849. (n) Li, H.; Wang, J.; E-Nunu, T.; Zu, L.; Jiang, W.; Wei, S.; Wang, W. Chem. Commun. 2007, 507. (o) Li, H.; Wang, J.; Xie, H.; Zu, L.; Jiang, W.; Duesler, E. N.; Wang, W. Org. Lett. 2007, 9, 965. (p) Li, H.; Zu. L.; Xie, H.; Wang, J.; Jiang, W.; Wang, W. Org. Lett. 2007, 9, 1833. (q) For a review, see: Palomo, C.; Mielgo, A. Angew. Chem., Int. Ed. 2006, 45, 7876. 2860
variety of natural products.7 The selective formation of the exo-isomer has long proven to be difficult.8 For instance, the Diels-Alder reactions of cyclopentadiene with acrolein, methyl acrylate, and methyl vinyl ketone all afford predominantly the endo-isomer. This endo-selectivity is enhanced by Lewis acid.9 Even in the recently developed Diels-Alder reaction catalyzed by organocatalyst,10 selective formation of the exo-isomer can be a challenging problem; MacMillan reported the first asymmetric Diels-Alder reaction catalyzed by organocatalyst of cyclopentadiene and R,β-unsaturated aldehydes which proceeded with excellent enantioselectivity in spite of low diastereoselectivity.10a On the other hand, Maruoka and co-workers reported an elegant exo- and enantioselective Diels-Alder reaction catalyzed by binaphthyl-based diamine salts.10h While excellent exo- and enantioselectivities were achieved, the scope was limited to cyclopentadiene and three R,β-unsaturated aldehydes. Development of an exo-selective and enantioselective DielsAlder reaction of wider generality is desirable. In this paper, we will disclose such a reaction using the catalyst diarylprolinol silyl ether. As a model we studied the reaction of cinnamaldehyde and cyclopentadiene in the presence of several diarylprolinol silyl ethers (results summarized in Table 1). As we have reported, in the presence of p-nitrophenol the tert-butyldimethylsilyl ether of diphenylprolinol (1) is an effective catalyst of an enantioselective ene reaction, affording the cyclopentadiene derivative 4 with excellent enantioselectivity (Scheme 1).5b However when the reaction was performed under acidic conditions, its course changed dramatically. When cinnamaldehyde and cyclopentadiene were treated with catalyst 1 in the presence of CF3CO2H in toluene, the cyclopentadiene derivative 4 was not formed but rather Diels-Alder adduct (7) For recent reviews of enantioselective Diels-Alder reactions: (a) Evans, D. A.; Johnson, J. S. In ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 1999; Vol. 3, p 1177. (b) Oppolzer, W. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 5. (c) Kagan, H. B.; Riant, O. Chem. ReV. 1992, 92, 1007. (d) Diaz, L. C.; Braz. J. Chem. Soc. 1997, 8, 289. (e) Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650. (f) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G. Angew. Chem., Int. Ed. 2002, 41, 1668. (g) Hayashi, Y. Catalytic Asymmetric Diels-Alder Reactions. In Cycloaddition Reaction in Organic Synthesis; Kobayashi, S., Jørgensen, K.A., Eds.; Wiley-VCH: Weinheim, Germany, 2002; pp 5-55. (8) (a) Gouverneur, V. E.; Houk, K. N.; de Pascual-Teresa, B.; Beno, B.; Janda, K. D.; Lerner, R. A. Science 1993, 262, 204. (b) Powers, T. S.; Jiang, W.; Su, J.; Wulff, W. D.; Waltermire, B. E.; Rheingold, A. L. J. Am. Chem. Soc. 1997, 119, 6438. (c) Maruoka, K.; Imoto, H.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 12115. (d) Kundig, E. P.; Saudan, C. M.; Alezra, V.; Viton, F.; Bernardinelli, G. Angew. Chem., Int. Ed. 2001, 40, 4481. (e) Cavill, J. L.; Peters, J.-U.; Tomkinson, N. C. O. Chem. Commun. 2003, 728. (9) Smith, M. B.; March, J. March’s AdVanced Organic Chemistry, 5th ed.; John Wiley & Sons, Inc.: New York, 2001; pp 1062-1075. (10) (a) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243. (b) Northup, A. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 2458. (c) Ishihara, K.; Nakano, K. J. Am. Chem. Soc. 2005, 127, 10504. (d) Wilson, R. M.; Jen, W. S.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 11616. (e) Kim, K. H.; Lee, S.; Lee, D.W.; Ko, D.-H.; Ha, D.-C. Tetrahedron Lett. 2005, 46, 5991. (f) Lemay, M.; Ogilvie, W. W. Org. Lett. 2005, 7, 4141. (g) Sakakura, A.; Suzuki, K.; Nakano, K.; Ishihara, K. Org. Lett. 2006, 8, 2229. (h) Kano, T.; Tanaka, Y.; Maruoka, K. Org. Lett. 2006, 8, 2687. (i) Sakakura, A.; Suzuki, K.; Ishihara, K. AdV. Synth. Catal. 2006, 348, 2457.
Org. Lett., Vol. 9, No. 15, 2007
Table 1. Effect of the Catalyst in the Reaction of Cinnamaldehyde and Cyclopentadiene Catalyzed by Organocatalystsa
entry
catalyst
additive
1 2 3 4 5 6 7 8 9
1 2 2 2 2 2 2 2 3
CF3CO2H none CH3CO2H CCl3CO2H CF3CO2H CSA TsOH‚H2O TfOH CF3CO2H
yield [%]b 10 0 0 69 86 10 13 0 80
Table 2. Enantioselective Diels-Alder Reaction between Cyclopentadiene and R,β-Unsaturated Aldehydes Catalyzed by Diarylprolinol Silyl Ether 3a
exo/endoc
ee (exo) [%]d
ee (endo) [%]d
79:21
79
88
87:13 84:16 57:43 88:12
95 95 69 45
79 83 5 0
85:15
97
88
entry
R
time [h]
1 2 3 4 5 6f 7 8 9g 10h
Ph 2-Np o-MeOPh p-BrPh p-NO2Ph 2-furyl cyclohexyl n-Bu CO2Et p-NO2Ph
26 28 78 24 6 100 17 3 17 17
yield [%]b
exo/endoc
quant 94 71 quant 93 67 78 65 92 quant
85:15 86:14 78:22 86:14 87:13 80:20 85:15 78:22 70:30 86:14
ee (exo) [%]d
ee (endo) [%]d
97 (2S)e 96 96 96 96 94 (2S)e 97 94 84 94
88 (2S)e 82 96 84 82 78 (2S)e 93 91 64 73
a
Unless otherwise shown, the reaction was conducted with 0.07 mmol of catalyst, 0.14 mmol of additive, 0.7 mmol of cinnamaldehyde, and 2.1 mmol of cyclopentadiene at rt. b Isolated yield of a mixture of 5-exo and 5-endo. c Determined by 1H NMR. d Determined by chiral HPLC analysis.
5 was obtained in good optical purity in spite of the low yield (Table 1, entry 1). Moreover, the exo-isomer was obtained predominantly. Catalyst, solvent, and additive were screened: 3,5-bis(trifluoromethyl)phenyl-substituted catalyst 2 was found to be a superior Diels-Alder reaction catalyst to diphenyl analogue 1. Several acids were investigated as additives including CH3CO2H, CCl3CO2H, CF3CO2H, camphorsulfonic acid, TsOH‚H2O, and TfOH. The reaction did not proceed in the presence of a weak acid such as CH3CO2H nor a strong acid such as TfOH, and of these, CF3CO2H was found to be most effective (entry 5). In marked contrast, no reaction proceeded in the presence of CH3CO2H (entry 3). Screening of the solvent indicated that toluene is suitable. The effect of the silyl group substituent was also investigated. Triethylsilyl derivative 3 gave higher enantioselectivity than the corresponding trimethylsilyl derivative 2. Results under the best reaction conditions are as follows: When a mixture of cinnamaldehyde and cyclopentadiene was treated with triethylsilyl ether 3 in the presence of CF3CO2H in toluene, the Diels-Alder product 5 was obtained in 80% yield with high exo-selectivity (exo/endo ) 85:15) and excellent enantioselectivity (exo 97% ee, endo 88% ee, entry 9). As the best conditions for the Diels-Alder reaction had been found, the generality of the reaction was investigated (results summarized in Table 2). Not only phenyl, but also a 2-naphthyl-substituted acrolein derivative gave an excellent result (entry 2). Although the reaction is slow for acrolein derivatives possessing electron-rich aromatic substituents such as o-methoxyphenyl, a good yield was obtained by prolonging the reaction time, high exo-selectivity and excelOrg. Lett., Vol. 9, No. 15, 2007
a Unless otherwise shown, the reaction was conducted with 0.07 mmol of catalyst 3, 0.14 mmol of CF3CO2H, 0.7 mmol of cinnamaldehyde, and 2.1 mmol of cyclopentadiene at rt in toluene. b Isolated yield of a mixture of exo and endo isomers. c Determined by 1H NMR (400-MHz). d The ee was determined by chiral HPLC or GC analysis. e Absolute configuration, see reference 10a. f Catalyst 3 (20 mol %) and CF3CO2H (40 mol %) were used. g The reaction was performed at 4 °C. h Catalyst 3 (2 mol %) and CF3CO2H (4 mol %) were used.
lent enantioselectivity were realized (entry 3). When the substituent is electron-deficient, such as p-bromophenyl and p-nitrophenyl, the reaction is fast, with high diastereo- and excellent enantioselectivities (entries 4, 5). Not only aromatic groups, but also heteroaromatic groups such as furyl are suitable substituents (entry 6). Alkyl group-substituted acrolein also gave good results, and steric size does not compromise the enantioselectivity (entries 7, 8). 3-Ethoxycarbonylpropenal is also a suitable R,β-unsaturated aldehyde, affording high selectivity (entry 9). Though we have used 10 mol % of the catalyst in the above reactions, loading can be reduced to 2 mol %. That is, in the presence of 2 mol % of 3 and 4 mol % of CF3CO2H, the reaction proceeds efficiently, affording the Diels-Alder product in 99% yield with excellent enantioselectivity (exo 94% ee, endo 73% ee, entry 10). Other dienes can also be employed successfully. Acyclic dienes such as 2,3-dimethyl-1,3-butadiene and isoprene are suitable dienes, producing the Diels-Alder products, also with excellent enantioselectivity as shown in Table 3. In the reaction of isoprene, there is the possibility that regio-isomers will be formed, but only a single isomer 7 was observed.11 The absolute configuration of 6 was determined by transformation to the known (1S, 6S)-(3,4-dimethyl-(6-hydroxymethyl)cyclohex-3-enyl)methanol.12 (11) The regiochemistry was determined by 2D-1H-NMR. (12) Bauer, T.; Chapuis, C.; Kucharska, A.; Rzepecki, P.; Jurczak, J. HelV. Chim. Acta 1998, 81, 324. 2861
Table 3. Enantioselective Diels-Alder Reaction between β-Ethoxycarbonylacrolein and Dienes Catalyzed by Diarylprolinol Silyl Ether 3a
known that chiral oxazaborolidinium ions prepared from diarylprolinol are versatile enantioselective Diels-Alder catalysts,2 it is interesting to note that after appropriate modification the same small molecule, diarylprolinol, can act both as part of a Lewis acid catalyst and as an organocatalyst in the asymmetric Diels-Alder reaction. Acknowledgment. This paper is dedicated to Prof. E. J. Corey for his elegant contributions to the chemistry of diphenyl prolinol. This work was partially supported by the Toray Science Foundation and a Grand-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science, and Technology (MEXT).
a Unless otherwise shown, the reaction was conducted with 0.07 mmol of catalyst 3, 0.14 mmol of CF3CO2H, 0.7 mmol of cinnamaldehyde, and 2.1 mmol of diene at 4 °C. b Isolated yield. c The ee was determined by chiral HPLC analysis.
In summary, we have developed an exo-selective DielsAlder reaction of R,β-unsaturated aldehdyes catalyzed by diarylprolinol silyl ether 3 under acidic conditions. As it is
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Supporting Information Available: Detailed experimental procedures, full characterization, copies of 1H-, 13C NMR and IR spectra of all new compounds. This material is available free of charge via the Internet at http://pubs.acs.org. OL071009+
Org. Lett., Vol. 9, No. 15, 2007
